Lipocalin 2 expression is associated with aggressive features of endometrial cancer
Lipocalin 2 expression is associated with aggressive features of endometrial cancer
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DOI：
10.1186/1471-2407-12-169
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发表时间：
2012-05-06
期刊：
影响因子：
3.8
通讯作者：
Akslen, Lars A.
中科院分区：
文献类型：
--
作者：
Mannelqvist, Monica;Stefansson, Ingunn M.;Akslen, Lars A.
背景：在几种癌症中观察到脂质运载蛋白2（LCN 2）表达增加。本研究的目的是探讨LCN 2在子宫内膜癌的临床病理表型，血管生成，上皮间质转化（EMT）的标志物，和patient survival.Methods：免疫组化染色进行使用人类LCN 2抗体对一个基于人口的一系列子宫内膜癌患者收集在霍达兰县（挪威）在1981-1990年（n = 256）。患者从初次手术开始随访至死亡或2007年末次随访。幸存者的中位随访时间为17年。来自前瞻性收集的子宫内膜癌系列（n = 76）和公开可用的子宫内膜癌系列（n = 111）的基因表达数据用于基因相关性研究。49%的病例中发现LCN 2蛋白表达与非类腺瘤组织学类型相关001）、核等级3（p = 0.001）、>50%实体瘤生长（p = 0.001）、ER和PR阴性（p = 0.028和0.006）和阳性EZH 2表达（p < 0.001）。LCN 2表达与VEGF-A表达显著相关（p = 0.021），尽管与所检查的其他血管生成标志物（血管增殖指数、肾小球样微血管增殖、VEGF-C、VEGF-D或bFGF 2表达）无关。此外，LCN 2与几种EMT相关标志物（E-钙粘蛋白、N-钙粘蛋白、P-钙粘蛋白、β-连环蛋白）无关，也与血管侵袭（肿瘤细胞侵入淋巴管或血管）无关。值得注意的是，LCN 2与远处肿瘤复发以及转移相关基因的S100 A家族显著相关。无LCN 2表达的肿瘤患者的5年生存率最高，为81%，而中等水平的患者为73%，LCN 2强染色的小亚组为38%（p = 0.007）。在多因素分析中，LCN 2表达是一个独立的预后因素，除了组织学分级和FIGO分期。结论：LCN 2表达增加与子宫内膜癌的侵袭性和预后不良。
Background: Increased expression of lipocalin 2 (LCN2) has been observed in several cancers. The aim of the present study was to investigate LCN2 in endometrial cancer in relation to clinico-pathologic phenotype, angiogenesis, markers of epithelial-mesenchymal transition (EMT), and patient survival.Methods: Immunohistochemical staining was performed using a human LCN2 antibody on a population-based series of endometrial cancer patients collected in Hordaland County (Norway) during 1981-1990 (n = 256). Patients were followed from the time of primary surgery until death or last follow-up in 2007. The median follow-up time for survivors was 17 years. Gene expression data from a prospectively collected endometrial cancer series (n = 76) and a publicly available endometrial cancer series (n = 111) was used for gene correlation studies.Results: Expression of LCN2 protein, found in 49% of the cases, was associated with non-endometrioid histologic type (p = 0.001), nuclear grade 3 (p = 0.001), >50% solid tumor growth (p = 0.001), ER and PR negativity (p = 0.028 and 0.006), and positive EZH2 expression (p < 0.001). LCN2 expression was significantly associated with expression of VEGF-A (p = 0.021), although not with other angiogenesis markers examined (vascular proliferation index, glomeruloid microvascular proliferation, VEGF-C, VEGF-D or bFGF2 expression). Further, LCN2 was not associated with several EMT-related markers (E-cadherin, N-cadherin, P-cadherin, beta-catenin), nor with vascular invasion (tumor cells invading lymphatic or blood vessels). Notably, LCN2 was significantly associated with distant tumor recurrences, as well as with the S100A family of metastasis related genes. Patients with tumors showing no LCN2 expression had the best outcome with 81% 5-year survival, compared to 73% for intermediate and 38% for the small subgroup with strong LCN2 staining (p = 0.007). In multivariate analysis, LCN2 expression was an independent prognostic factor in addition to histologic grade and FIGO stage.Conclusion: Increased LCN2 expression is associated with aggressive features and poor prognosis in endometrial cancer.